Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour
Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour
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DOI：
10.1136/jmg.2004.022673
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发表时间：
2005-02-01
影响因子：
4
通讯作者：
Rahman, N
中科院分区：
文献类型：
--
作者：
Reid, S;Renwick, A;Rahman, N
方法家系报告WILMS 2作为我们对WT易感性研究的一部分，经伦敦多中心研究伦理委员会批准。这个家庭包括两个患有WT的兄弟。大孩子第一次引起注意时，他的隐睾症是在2岁时纠正的。当时，观察到色素减退和色素沉着区域以及一些咖啡色Au Lait斑点，其体重、身高和头围低于第3百分位数。在3.5岁时，一个III期WT被手术切除，在用长春新碱和放线菌素D进行放疗和化疗后，这个孩子顺利康复。在9岁时，他出现癫痫发作，并被发现有两个脑内病变，立体定向活检诊断为多形性胶质母细胞瘤。由于疾病广泛，没有尝试进一步的手术，孩子在13个月后死亡。第二个儿子出生时很顺利，婴儿期很早，身高和体重正常，但他有三个咖啡色Au lait斑点和许多小的色素脱失和色素沉着过度的斑点。在7个月时，诊断为1期WT并手术切除，给予放线菌素D，未进行放疗。5年后，虽然无症状，但鉴于家族史，进行MRI脑部扫描作为筛查程序。小脑病变被确定和切除。组织学检查证实为IV级髓母细胞瘤，采用放疗治疗。在10岁时，他发展为前B细胞急性淋巴细胞白血病，并注意到染色体自发断裂。他接受了化疗，并因天冬酰胺酶而发生脑出血。他随后死于12岁的弥漫性复发的髓母细胞瘤。
METHODS Family report WILMS2 was ascertained as part of our research on susceptibility to WT, which is approved by the London Multicentre Research Ethics Committee. The family includes two affected brothers with WT. The elder child first came to attention when his cryptorchidism was corrected at 2 years of age. At that time hypo-and hyperpigmented areas and a few café au lait spots were noted and he was below the 3rd centile for weight, height, and head circumference. At 3.5 years of age a stage III WT was surgically removed and the child made an uneventful recovery after radiotherapy and chemotherapy with vincristine and actinomycin D. At 9 years of age he developed seizures and was found to have two intracerebral lesions, which were diagnosed as glioblastoma multiforme on stereotactic biopsy. Due to extensive disease no further surgery was attempted and the child died 13 months later. The second son had an uneventful birth and early infancy with normal height and weight, though he was noted to have three café au lait spots and many small depigmented and hyperpigmented spots. At 7 months a stage 1 WT was diagnosed and surgically removed and he was given actinomycin D without radiotherapy. Then 5 years later, whilst asymptomatic, an MRI brain scan was performed as a screening procedure in view of the family history. A cerebellar lesion was identified and resected. Histology confirmed a grade IV medulloblastoma which was treated with radiotherapy. At 10 years of age he developed pre B cell acute lymphoblastic leukaemia and spontaneous breakages of the chromosomes was noted. He was treated with chemotherapy and suffered a cerebral haemorrhage due to asparaginase. He subsequently died at 12 years of age from diffuse relapse of the medulloblastoma.